Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

一种新的密码本原:棘轮密钥交换的定义、模型及构造

在传统密码学应用中,人们总假定终端是安全的,并且敌手只存在于通信信道上。然而,主流的恶意软件和系统漏洞给终端安全带来了严重和直接的威胁和挑战,例如容易遭受存储内容被病毒破坏、随机数发生器被腐化等各种攻击。更糟糕的是,协议会话通常有较长的生存期,因此需要在较长的时间内存储与会话相关的秘密信息。在这种情况下,有必要设计高强度的安全协议,以对抗可以暴露存储内容和中间计算结果(包括随机数)的敌手。棘轮密钥交换是解决这一问题的一个基本工具。文中综述了密码本原——棘轮密钥交换,包括单向、半双向和双向等棘轮密钥交换的定义、模型及构造,并展望了棘轮密钥交换的未来发展趋势。     

潼湖特大桥跨潮莞高速(88+160+88)m连续刚构关键施工技术

随着交通的日益发展,大跨度跨线连续刚构桥梁修建越来越多。本文结合潼湖特大桥跨潮莞高速(88+160+88)m连续刚构施工的成功实践,详细阐述了该桥的施工关键及其梁体施工的线型控制,跨既有公路施工防护及混凝土施工等关键施工技术,可供类似工程参考。     

Low area field-programmable gate array implementation of PRESENT image encryption with key rotation and substitution

Lightweight ciphers are increasingly employed in cryptography because of the high demand for secure data transmission in wireless sensor network, embedded devices, and Internet of Things. The PRESENT algorithm as an ultra-lightweight block cipher provides better solution for secure hardware cryptography with low power consumption and minimum resource. This study generates the key using key rotation and substitution method, which contains key rotation, key switching, and binary-coded decimal-based key generation used in image encryption. The key rotation and substitution-based PRESENT architecture is proposed to increase security level for data stream and randomness in cipher through providing high resistance to attacks. Lookup table is used to design the key scheduling module, thus reducing the area of architecture. Field-programmable gate array (FPGA) performances are evaluated for the proposed and conventional methods. In Virtex 6 device, the proposed key rotation and substitution PRESENT architecture occupied 72 lookup tables, 65 flip flops, and 35 slices which are comparably less to the existing architecture.     

一种标准模型下无证书签名方案的安全性分析与改进

无证书签名具有基于身份密码体制和传统公钥密码体制的优点，可解决复杂的公钥证书管理和密钥托管问题.Wu和Jing提出了一种强不可伪造的无证书签名方案，其安全性不依赖于理想的随机预言机.针对该方案的安全性，提出了两类伪造攻击.分析结果表明，该方案无法实现强不可伪造性，并在"malicious-but-passive"的密钥生成中心攻击下也是不安全的.为了提升该方案的安全性，设计了一个改进的无证书签名方案.在标准模型中证明了改进的方案对于适应性选择消息攻击是强不可伪造的，还能抵抗恶意的密钥生成中心攻击.此外，改进的方案具有较低的计算开销和较短的私钥长度，可应用于区块链、车联网、无线体域网等领域.     

A New NTRU-Type Public-Key Cryptosystem over the Binary Field

As the development of cloud computing and the convenience of wireless sensor netowrks, smart devices are widely used in daily life, but the security issues of the smart devices have not been well resolved. In this paper, we present a new NTRU-type public-key cryptosystem over the binary field. Specifically, the security of our scheme relies on the computational intractability of an unbalanced sparse polynomial ratio problem (DUSPR). Through theoretical analysis, we prove the correctness of our proposed cryptosystem. Furthermore, we implement our scheme using the NTL library, and conduct a group of experiments to evaluate the capabilities and consuming time of encryption and decryption. Our experiments result demonstrates that the NTRU-type public-key cryptosystem over the binary field is relatively practical and effective.     

Title加TextRank抽取关键句的情感分类研究

考虑到不同句子对判断文档情感倾向的重要程度不同，因而区分文档的关键句和细节句将有助于提高情感分类的性能。同时，考虑到Title和上下文信息，提出了一种基于Title和加权TextRank抽取关键句的情感分析方法SKTT，实现了高效的情感分析。根据文档Title的情感权重计算Title贡献度，考虑到标点和语义规则对情感倾向的影响；根据加权TextRank算法思想，在文档正文中构建了一个情感句有向图来提取关键句；计算所有关键句的情感倾向进行情感分类。在4个领域上进行实验，实验结果表明，该SKTT方法性能明显优于Baseline，具有高效性。     

硬质道路石油沥青关键组分的研制

筛选出适合制备硬质道路石油沥青关键组分的减压渣油，并以此为原料，考察了蒸馏深拔、深度氧化及溶剂脱沥青工艺制备的硬质道路沥青关键组分的性能。所制备的关键组分能够大幅提升基质沥青的高温性能，且通用性好；将关键组分与基质沥青按适合比例调合可以稳定生产高温性能好的硬质道路石油沥青，其混合料耐高温性能好。同时,为便于硬质沥青关键组分的使用,还开发了关键组分的造粒成型技术,提出其适于成型造粒的黏度范围为0.6～6 Pa?S。采用关键组分生产的硬质道路沥青用于高速公路实体工程，经过2年以上的气候和通车考验，沥青路面无车辙、无开裂，保持优良的使用性能。     

HACCP在浓香菜籽油生产中的应用

为了保障浓香菜籽油的产品质量安全,采用HACCP体系对浓香菜籽油生产全过程进行生物、物理、化学的危害分析,确定关键控制点,制定预防措施,并对生产环节进行有效监控,制定纠偏措施,做好记录管理,为浓香菜籽油的安全生产提供借鉴。     

基于关键拓扑变动项辨识的调度操作潮流校核方法

为解决传统调度操作潮流校核中的有效性问题，定义了一种面向调度操作的关键拓扑变动概念，提出并实现了基于关键拓扑变动辨识的调度操作潮流校核方法。首先，剖析了调度操作安全校核的实施目的，围绕其运行断面潮流校验的校核目的，定义了面向调度操作的关键拓扑变动概念，并基于网络拓扑连接关系设计了其辨识方法。在此基础上，提出了基于关键拓扑变动项辨识的调度操作潮流校核方法，明确了其实施流程和要点。最后基于当前电网调度自动化系统实际，构建了其实施框架，并介绍了其在某电网的实施效益。